The principal aims are to gain a broader understanding of the pathophysiology of immune hemolysis, particularly autoimmune hemolysis, and to determine the relationship of these phenomena to coexisting malignant disease. The work will be concerned with: 1) study of variables in a recently developed quantitative assay for anti-C3d antibody concentrations and equilibrium constants, 2) definition of the combining ratio of anti-C3d with RBC-bound C3d, 3) development of labeled antibody methods for quantitating C3d bound to RBC (employing labeled rabbit anti-C3d and employing unlabeled rabbit anti-C3d followed by labeled goat or sheep anti-rabbit-IgG), 4) definition of conditions for reproducible preparation of strongly and weakly C3d-coated RBC suitable for standardization of anti-C3d reagents, 5) application of labeled antibody quantitation of C3d bound to RBC of normal subjects, selected patients without malignancy or autoimmune hemolytic anemia (AHA), patients with primary AHA or AHA secondary to non-malignant diseases, patients with malignancies with or without associated AHA. Additional studies will entail: 1) use of anti-C4d reagents to determine how often in vivo RBC C3d-coating occurs via the alternative pathway of complement activation, 2) attempts to confirm complement binding by anti-Rh(D) antibodies, 3) relation of bound C3d on normal RBC to cell age, 4) application of labeled antibody methods to selected cross-matching problems, 5) application of labeled antibody methods to investigation of suspected delayed incompatible transfusion reactions, (6) investigation of the incidence of elevated cold agglutinins in non-lymphoreticular malignancies, autoimmune diseases (not primarily hematologic), and pregnancy, 7) continuing studies of alterations in coagulation factors in relation to painful sickle cell crises, and 8) special studies of unusual examples of alloimmune and autoimmune hemolysis.